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image of Regulatory Relationships between DNA Methylation and Long Non- coding RNAs in Neuroblastoma

Abstract

Objectives

Neuroblastoma (NB) is a prevalent pediatric solid malignancy associated with significant morbidity and mortality, largely driven by epigenetic alterations. This review aims to identify novel biomarkers related to long non-coding RNAs (lncRNAs) and DNA methylation in NB to enhance prognostic capabilities.

Methods

We conducted a detailed analysis of the interplay between lncRNAs and DNA methylation in NB, focusing on regulatory variations and their implications for disease progression. Key lncRNAs, including GTL2/MEG3, DALI, NBAT-1, and DLX6-AS1, were examined for their regulation by DNA methylation through cis- and trans-methylation mechanisms.

Results

There are clinical and biological implications of lncRNAs in NB and related cancers. Notably, GTL2 and its alias MEG3 are implicated in tumorigenesis through epigenetic modifications, such as hypermethylation, leading to the loss of gene expression and aggressive tumor behavior. Similarly, the interactions of DALI with adjacent genes illustrate the crucial role lncRNAs play in neuronal differentiation and tumor progression, suggesting their potential to impact prognosis through regulatory effects. Furthermore, NBAT-1 emerges as a promising tumor suppressor with strong correlations to NB prognosis, where its methylation-induced silencing is associated with negative outcomes. DLX6-AS1 is also linked to increased NB risk, with expression patterns correlating to disease stage and survival rates; however, more extensive survival data are required to establish its prognostic value.

Conclusion

This review highlights the potential of lncRNAs as prognostic indicators in NB, emphasizing the need for further research to elucidate their roles and validate them as biomarkers for improved patient outcomes.

© 2025 Bentham Science Publishers
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2025-04-23
2025-11-04

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References

  1. Tsubota S. Kadomatsu K. Origin and initiation mechanisms of neuroblastoma. Cell Tissue Res. 2018 372 2 211 221 10.1007/s00441‑018‑2796‑z 29445860
    [Google Scholar]
  2. Schulte J.H. Eggert A. Neuroblastoma. Crit. Rev. Oncog. 2015 20 3-4 245 270 10.1615/CritRevOncog.2015014033 26349419
    [Google Scholar]
  3. Mahapatra S. Challagundla K.B. Neuroblastoma. StatPearls. Treasure Island (FL) StatPearls Publishing 2023 1 6 28846355
    [Google Scholar]
  4. Brodeur G.M. Spontaneous regression of neuroblastoma. Cell Tissue Res. 2018 372 2 277 286 10.1007/s00441‑017‑2761‑2 29305654
    [Google Scholar]
  5. Davidoff A.M. Neuroblastoma. Semin. Pediatr. Surg. 2012 21 1 2 14 10.1053/j.sempedsurg.2011.10.009 22248965
    [Google Scholar]
  6. Basta N.O. Halliday G.C. Makin G. Birch J. Feltbower R. Bown N. Elliott M. Moreno L. Barone G. Pearson A.D.J. James P.W. Tweddle D.A. McNally R.J.Q. Factors associated with recurrence and survival length following relapse in patients with neuroblastoma. Br. J. Cancer 2016 115 9 1048 1057 10.1038/bjc.2016.302 27701387
    [Google Scholar]
  7. Cheung N.K.V. Dyer M.A. Neuroblastoma: Developmental biology, cancer genomics and immunotherapy. Nat. Rev. Cancer 2013 13 6 397 411 10.1038/nrc3526 23702928
    [Google Scholar]
  8. Ning B.T. Yu B. Chan S. Chan J. Huang J.D. Chan G.C.F. Treatment of neuroblastoma with an engineered “obligate” anaerobic Salmonella typhimurium strain YB1. J. Cancer 2017 8 9 1609 1618 10.7150/jca.18776 28775780
    [Google Scholar]
  9. Bartholomew J. Washington T. Bergeron S. Nielson D. Saggio J. Quirk L. Dinutuximab. J. Pediatr. Oncol. Nurs. 2017 34 1 5 12 10.1177/1043454216659448 27456981
    [Google Scholar]
  10. Burmakin M. Shi Y. Hedström E. Kogner P. Selivanova G. Dual targeting of wild-type and mutant p53 by small molecule RITA results in the inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in vivo and in vitro. Clin. Cancer Res. 2013 19 18 5092 5103 10.1158/1078‑0432.CCR‑12‑2211 23864164
    [Google Scholar]
  11. Kushner B.H. Cheung N.K.V. Modak S. Becher O.J. Basu E.M. Roberts S.S. Kramer K. Dunkel I.J. A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma. Int. J. Cancer 2017 140 2 480 484 10.1002/ijc.30440 27649927
    [Google Scholar]
  12. Mossé Y.P. Lim M.S. Voss S.D. Wilner K. Ruffner K. Laliberte J. Rolland D. Balis F.M. Maris J.M. Weigel B.J. Ingle A.M. Ahern C. Adamson P.C. Blaney S.M. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: A Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013 14 6 472 480 10.1016/S1470‑2045(13)70095‑0 23598171
    [Google Scholar]
  13. Peirce S.K. Findley H.W. Prince C. Dasgupta A. Cooper T. Durden D.L. The PI-3 kinase-Akt-MDM2-survivin signaling axis in high-risk neuroblastoma: A target for PI-3 kinase inhibitor intervention. Cancer Chemother. Pharmacol. 2011 68 2 325 335 10.1007/s00280‑010‑1486‑7 20972874
    [Google Scholar]
  14. Perwein T. Lackner H. Sovinz P. Benesch M. Schmidt S. Schwinger W. Urban C. Survival and late effects in children with stage 4 neuroblastoma. Pediatr. Blood Cancer 2011 57 4 629 635 10.1002/pbc.23036 21319289
    [Google Scholar]
  15. Capasso M. Diskin S.J. Genetics and genomics of neuroblastoma. Cancer Treat. Res. 2010 155 65 84 10.1007/978‑1‑4419‑6033‑7_4 20517688
    [Google Scholar]
  16. Diskin S.J. Capasso M. Diamond M. Oldridge D.A. Conkrite K. Bosse K.R. Russell M.R. Iolascon A. Hakonarson H. Devoto M. Maris J.M. Rare variants in TP53 and susceptibility to neuroblastoma. J. Natl. Cancer Inst. 2014 106 4 dju047 10.1093/jnci/dju047 24634504
    [Google Scholar]
  17. Oldridge D.A. Wood A.C. Weichert-Leahey N. Crimmins I. Sussman R. Winter C. McDaniel L.D. Diamond M. Hart L.S. Zhu S. Durbin A.D. Abraham B.J. Anders L. Tian L. Zhang S. Wei J.S. Khan J. Bramlett K. Rahman N. Capasso M. Iolascon A. Gerhard D.S. Auvil J.M.G. Young R.A. Hakonarson H. Diskin S.J. Look A.T. Maris J.M. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature 2015 528 7582 418 421 10.1038/nature15540 26560027
    [Google Scholar]
  18. Sharma R. Mer J. Lion A. Vik T.A. Clinical presentation, evaluation, and management of neuroblastoma. Pediatr. Rev. 2018 39 4 194 203 10.1542/pir.2017‑0087 29610427
    [Google Scholar]
  19. Yang T. Zhang Z. Zhang J. Tan T. Yang J. Pan J. Hu C. Li J. Xia H. He J. Zou Y. The rs2147578 C > G polymorphism in the Inc-LAMC2–1:1 gene is associated with increased neuroblastoma risk in the Henan children. BMC Cancer 2018 18 1 948 10.1186/s12885‑018‑4847‑y 30285664
    [Google Scholar]
  20. Chi Y. Wang D. Wang J. Yu W. Yang J. Long non-coding RNA in the pathogenesis of cancers. Cells 2019 8 9 1015 10.3390/cells8091015 31480503
    [Google Scholar]
  21. Fang Y. Fullwood M.J. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Geno. Prot. Bioinfor. 2016 14 1 42 54 10.1016/j.gpb.2015.09.006 26883671
    [Google Scholar]
  22. Schmitt A.M. Chang H.Y. Long non-coding RNAs in cancer pathways. Cancer Cell 2016 29 4 452 463 10.1016/j.ccell.2016.03.010 27070700
    [Google Scholar]
  23. Buechner J. Einvik C. N-myc and non-coding RNAs in neuroblastoma. Mol. Cancer Res. 2012 10 10 1243 1253 10.1158/1541‑7786.MCR‑12‑0244 22936790
    [Google Scholar]
  24. Charlet J. Tomari A. Dallosso A.R. Szemes M. Kaselova M. Curry T.J. Almutairi B. Etchevers H.C. McConville C. Malik K.T.A. Brown K.W. Genome-wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma. Mol. Carcinog. 2017 56 4 1290 1301 10.1002/mc.22591 27862318
    [Google Scholar]
  25. Djos A. Martinsson T. Kogner P. Carén H. The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. Mol. Cancer 2012 11 1 40 10.1186/1476‑4598‑11‑40 22695170
    [Google Scholar]
  26. Gómez S. Castellano G. Mayol G. Suñol M. Queiros A. Bibikova M. Nazor K.L. Loring J.F. Lemos I. Rodríguez E. de Torres C. Mora J. Martín-Subero J.I. Lavarino C. DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights. Epigenomics 2015 7 7 1137 1153 10.2217/epi.15.49 26067621
    [Google Scholar]
  27. Prajapati B. Fatma M. Fatima M. Khan M.T. Sinha S. Seth P.K. Identification of lncRNAs associated with neuroblastoma in cross-sectional databases: Potential biomarkers. Front. Mol. Neurosci. 2019 12 293 10.3389/fnmol.2019.00293 31920530
    [Google Scholar]
  28. Astuti D. Latif F. Wagner K. Gentle D. Cooper W.N. Catchpoole D. Grundy R. Ferguson-Smith A.C. Maher E.R. Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: Analysis of neuroblastoma, phaeochromocytoma and Wilms’ tumour. Br. J. Cancer 2005 92 8 1574 1580 10.1038/sj.bjc.6602478 15798773
    [Google Scholar]
  29. Chalei V. Sansom S.N. Kong L. Lee S. Montiel J.F. Vance K.W. Ponting C.P. The long non-coding RNA Dali is an epigenetic regulator of neural differentiation. eLife 2014 3 e04530 10.7554/eLife.04530 25415054
    [Google Scholar]
  30. Olsson M. Beck S. Kogner P. Martinsson T. Carén H. Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors. Epigenetics 2016 11 1 74 84 10.1080/15592294.2016.1138195 26786290
    [Google Scholar]
  31. Pandey G.K. Mitra S. Subhash S. Hertwig F. Kanduri M. Mishra K. Fransson S. Ganeshram A. Mondal T. Bandaru S. Östensson M. Akyürek L.M. Abrahamsson J. Pfeifer S. Larsson E. Shi L. Peng Z. Fischer M. Martinsson T. Hedborg F. Kogner P. Kanduri C. The risk-associated long non-coding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell 2014 26 5 722 737 10.1016/j.ccell.2014.09.014 25517750
    [Google Scholar]
  32. Jones P.A. Baylin S.B. The epigenomics of cancer. Cell 2007 128 4 683 692 10.1016/j.cell.2007.01.029 17320506
    [Google Scholar]
  33. Qiu Y.Y. Mirkin B.L. Dwivedi R.S. Inhibition of DNA methyltransferase reverses cisplatin induced drug resistance in murine neuroblastoma cells. Cancer Detect. Prev. 2005 29 5 456 463 10.1016/j.cdp.2005.05.004 16185816
    [Google Scholar]
  34. Fulda S. Poremba C. Berwanger B. Häcker S. Eilers M. Christiansen H. Hero B. Debatin K.M. Loss of caspase-8 expression does not correlate with MYCN amplification, aggressive disease, or prognosis in neuroblastoma. Cancer Res. 2006 66 20 10016 10023 10.1158/0008‑5472.CAN‑05‑4079 17047064
    [Google Scholar]
  35. Bresler S.C. Weiser D.A. Huwe P.J. Park J.H. Krytska K. Ryles H. Laudenslager M. Rappaport E.F. Wood A.C. McGrady P.W. Hogarty M.D. London W.B. Radhakrishnan R. Lemmon M.A. Mossé Y.P. ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell 2014 26 5 682 694 10.1016/j.ccell.2014.09.019 25517749
    [Google Scholar]
  36. O’Donohue T. Gulati N. Mauguen A. Kushner B.H. Shukla N. Rodriguez-Sanchez M.I. Bouvier N. Roberts S. Basu E. Cheung N.K. Modak S. Differential impact of ALK mutations in neuroblastoma. JCO Precis. Oncol. 2021 5 5 492 500 10.1200/PO.20.00181 34250410
    [Google Scholar]
  37. Kawashima M. Kojima M. Ueda Y. Kurihara S. Hiyama E. Telomere biology including TERT rearrangements in neuroblastoma: A useful indicator for surgical treatments. J. Pediatr. Surg. 2016 51 12 2080 2085 10.1016/j.jpedsurg.2016.09.042 27793328
    [Google Scholar]
  38. Valentijn L.J. Koster J. Zwijnenburg D.A. Hasselt N.E. van Sluis P. Volckmann R. van Noesel M.M. George R.E. Tytgat G.A.M. Molenaar J.J. Versteeg R. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat. Genet. 2015 47 12 1411 1414 10.1038/ng.3438 26523776
    [Google Scholar]
  39. Cheung N.K.V. Zhang J. Lu C. Parker M. Bahrami A. Tickoo S.K. Heguy A. Pappo A.S. Federico S. Dalton J. Cheung I.Y. Ding L. Fulton R. Wang J. Chen X. Becksfort J. Wu J. Billups C.A. Ellison D. Mardis E.R. Wilson R.K. Downing J.R. Dyer M.A. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 2012 307 10 1062 1071 10.1001/jama.2012.228 22416102
    [Google Scholar]
  40. Molenaar J.J. Koster J. Zwijnenburg D.A. van Sluis P. Valentijn L.J. van der Ploeg I. Hamdi M. van Nes J. Westerman B.A. van Arkel J. Ebus M.E. Haneveld F. Lakeman A. Schild L. Molenaar P. Stroeken P. van Noesel M.M. Øra I. Santo E.E. Caron H.N. Westerhout E.M. Versteeg R. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 2012 483 7391 589 593 10.1038/nature10910 22367537
    [Google Scholar]
  41. Pugh T.J. Morozova O. Attiyeh E.F. Asgharzadeh S. Wei J.S. Auclair D. Carter S.L. Cibulskis K. Hanna M. Kiezun A. Kim J. Lawrence M.S. Lichenstein L. McKenna A. Pedamallu C.S. Ramos A.H. Shefler E. Sivachenko A. Sougnez C. Stewart C. Ally A. Birol I. Chiu R. Corbett R.D. Hirst M. Jackman S.D. Kamoh B. Khodabakshi A.H. Krzywinski M. Lo A. Moore R.A. Mungall K.L. Qian J. Tam A. Thiessen N. Zhao Y. Cole K.A. Diamond M. Diskin S.J. Mosse Y.P. Wood A.C. Ji L. Sposto R. Badgett T. London W.B. Moyer Y. Gastier-Foster J.M. Smith M.A. Auvil J.M.G. Gerhard D.S. Hogarty M.D. Jones S.J.M. Lander E.S. Gabriel S.B. Getz G. Seeger R.C. Khan J. Marra M.A. Meyerson M. Maris J.M. The genetic landscape of high-risk neuroblastoma. Nat. Genet. 2013 45 3 279 284 10.1038/ng.2529 23334666
    [Google Scholar]
  42. Fetahu I.S. Taschner-Mandl S. Neuroblastoma and the epigenome. Cancer Metastasis Rev. 2021 40 1 173 189 10.1007/s10555‑020‑09946‑y 33404859
    [Google Scholar]
  43. Abe M. Westermann F. Nakagawara A. Takato T. Schwab M. Ushijima T. Marked and independent prognostic significance of the CpG island methylator phenotype in neuroblastomas. Cancer Lett. 2007 247 2 253 258 10.1016/j.canlet.2006.05.001 16759796
    [Google Scholar]
  44. Bhan A. Soleimani M. Mandal S.S. Long non-coding RNA and cancer: A new paradigm. Cancer Res. 2017 77 15 3965 3981 10.1158/0008‑5472.CAN‑16‑2634 28701486
    [Google Scholar]
  45. Baldini F. Calderoni M. Vergani L. Modesto P. Florio T. Pagano A. An overview of long non-coding (lnc)RNAs in neuroblastoma. Int. J. Mol. Sci. 2021 22 8 4234 10.3390/ijms22084234 33921816
    [Google Scholar]
  46. Liu P.Y. Tee A.E. Milazzo G. Hannan K.M. Maag J. Mondal S. Atmadibrata B. Bartonicek N. Peng H. Ho N. Mayoh C. Ciaccio R. Sun Y. Henderson M.J. Gao J. Everaert C. Hulme A.J. Wong M. Lan Q. Cheung B.B. Shi L. Wang J.Y. Simon T. Fischer M. Zhang X.D. Marshall G.M. Norris M.D. Haber M. Vandesompele J. Li J. Mestdagh P. Hannan R.D. Dinger M.E. Perini G. Liu T. The long non-coding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35. Nat. Commun. 2019 10 1 5026 10.1038/s41467‑019‑12971‑3 31690716
    [Google Scholar]
  47. Sahu D. Hsu C.L. Lin C.C. Yang T.W. Hsu W.M. Ho S.Y. Juan H.F. Huang H.C. Co-expression analysis identifies long non-coding RNA SNHG1 as a novel predictor for event-free survival in neuroblastoma. Oncotarget 2016 7 36 58022 58037 10.18632/oncotarget.11158 27517149
    [Google Scholar]
  48. Wen Y. Gong X. Dong Y. Tang C. Long non coding RNA SNHG16 facilitates proliferation, migration, invasion and autophagy of neuroblastoma cells via sponging miR-542-3p and upregulating ATG5 expression. OncoTargets Ther. 2020 13 263 275 10.2147/OTT.S226915 32021273
    [Google Scholar]
  49. Li J. Li P. Zhao W. Yang R. Chen S. Bai Y. Dun S. Chen X. Du Y. Wang Y. Zang W. Zhao G. Zhang G. Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma. Cancer Cell Int. 2015 15 1 48 10.1186/s12935‑015‑0201‑5 26052251
    [Google Scholar]
  50. Mondal T. Juvvuna P.K. Kirkeby A. Mitra S. Kosalai S.T. Traxler L. Hertwig F. Wernig-Zorc S. Miranda C. Deland L. Volland R. Bartenhagen C. Bartsch D. Bandaru S. Engesser A. Subhash S. Martinsson T. Carén H. Akyürek L.M. Kurian L. Kanduri M. Huarte M. Kogner P. Fischer M. Kanduri C. Sense-antisense lncRNA pair encoded by locus 6p22.3 determines neuroblastoma susceptibility via the USP36-CHD7-SOX9 regulatory axis. Cancer Cell 2018 33 3 417 434.e7 10.1016/j.ccell.2018.01.020 29533783
    [Google Scholar]
  51. Pagano A. Castelnuovo M. Tortelli F. Ferrari R. Dieci G. Cancedda R. New small nuclear RNA gene-like transcriptional units as sources of regulatory transcripts. PLoS Genet. 2007 3 2 e1 10.1371/journal.pgen.0030001 17274687
    [Google Scholar]
  52. Castelnuovo M. Massone S. Tasso R. Fiorino G. Gatti M. Robello M. Gatta E. Berger A. Strub K. Florio T. Dieci G. Cancedda R. Pagano A. An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells. FASEB J. 2010 24 10 4033 4046 10.1096/fj.10‑157032 20581224
    [Google Scholar]
  53. Meng X. Fang E. Zhao X. Feng J. Identification of prognostic long non-coding RNAs associated with spontaneous regression of neuroblastoma. Cancer Med. 2020 9 11 3800 3815 10.1002/cam4.3022 32216054
    [Google Scholar]
  54. Arab K. Park Y.J. Lindroth A.M. Schäfer A. Oakes C. Weichenhan D. Lukanova A. Lundin E. Risch A. Meister M. Dienemann H. Dyckhoff G. Herold-Mende C. Grummt I. Niehrs C. Plass C. Long non-coding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol. Cell 2014 55 4 604 614 10.1016/j.molcel.2014.06.031 25087872
    [Google Scholar]
  55. Wang S.L. Huang Y. Su R. Yu Y.Y. Silencing long non-coding RNA HOTAIR exerts anti-oncogenic effect on human acute myeloid leukemia via demethylation of HOXA5 by inhibiting Dnmt3b. Cancer Cell Int. 2019 19 1 114 10.1186/s12935‑019‑0808‑z 31168296
    [Google Scholar]
  56. Deng J. Mueller M. Geng T. Shen Y. Liu Y. Hou P. Ramillapalli R. Taylor H.S. Paidas M. Huang Y. H19 lncRNA alters methylation and expression of Hnf4α in the liver of metformin-exposed fetuses. Cell Death Dis. 2017 8 12 e3175 10.1038/cddis.2017.392 29215608
    [Google Scholar]
  57. Fu Y. Wang W. Li X. Liu Y. Niu Y. Zhang B. Nie J. Pan B. Wang R. Yang J. LncRNA H19 interacts with S-adenosylhomocysteine hydrolase to regulate LINE-1 methylation in human lung-derived cells exposed to benzo[a]pyrene. Chemosphere 2018 207 84 90 10.1016/j.chemosphere.2018.05.048 29772428
    [Google Scholar]
  58. Zhou J. Yang L. Zhong T. Mueller M. Men Y. Zhang N. Xie J. Giang K. Chung H. Sun X. Lu L. Carmichael G.G. Taylor H.S. Huang Y. H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase. Nat. Commun. 2015 6 1 10221 10.1038/ncomms10221 26687445
    [Google Scholar]
  59. Zhi H. Li X. Wang P. Gao Y. Gao B. Zhou D. Zhang Y. Guo M. Yue M. Shen W. Ning S. Jin L. Li X. Lnc2Meth: A manually curated database of regulatory relationships between long non-coding RNAs and DNA methylation associated with human disease. Nucleic Acids Res. 2018 46 D1 D133 D138 10.1093/nar/gkx985 29069510
    [Google Scholar]
  60. Brioude F. Kalish J.M. Mussa A. Foster A.C. Bliek J. Ferrero G.B. Boonen S.E. Cole T. Baker R. Bertoletti M. Cocchi G. Coze C. De Pellegrin M. Hussain K. Ibrahim A. Kilby M.D. Krajewska-Walasek M. Kratz C.P. Ladusans E.J. Lapunzina P. Le Bouc Y. Maas S.M. Macdonald F. Õunap K. Peruzzi L. Rossignol S. Russo S. Shipster C. Skórka A. Tatton-Brown K. Tenorio J. Tortora C. Grønskov K. Netchine I. Hennekam R.C. Prawitt D. Tümer Z. Eggermann T. Mackay D.J.G. Riccio A. Maher E.R. Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: An international consensus statement. Nat. Rev. Endocrinol. 2018 14 4 229 249 10.1038/nrendo.2017.166 29377879
    [Google Scholar]
  61. Zhao J. Zhang X. Zhou Y. Ansell P.J. Klibanski A. Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response element (CRE) in the MEG3 proximal promoter region. Int. J. Biochem. Cell Biol. 2006 38 10 1808 1820 10.1016/j.biocel.2006.05.004 16793321
    [Google Scholar]
  62. Clark M.B. Mattick J.S. Long non-coding RNAs in cell biology. Semin. Cell Dev. Biol. 2011 22 4 366 376 10.1016/j.semcdb.2011.01.001 21256239
    [Google Scholar]
  63. Lipovich L. Johnson R. Lin C.Y. MacroRNA underdogs in a microRNA world: Evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochim. Biophys. Acta. Gene Regul. Mech. 2010 1799 9 597 615 10.1016/j.bbagrm.2010.10.001 20951849
    [Google Scholar]
  64. Zhang X. Zhou Y. Klibanski A. Isolation and characterization of novel pituitary tumor related genes: A cDNA representational difference approach. Mol. Cell. Endocrinol. 2010 326 1-2 40 47 10.1016/j.mce.2010.02.040 20211686
    [Google Scholar]
  65. Liao Q. Liu C. Yuan X. Kang S. Miao R. Xiao H. Zhao G. Luo H. Bu D. Zhao H. Skogerbø G. Wu Z. Zhao Y. Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network. Nucleic Acids Res. 2011 39 9 3864 3878 10.1093/nar/gkq1348 21247874
    [Google Scholar]
  66. Zhou Y. Zhong Y. Wang Y. Zhang X. Batista D.L. Gejman R. Ansell P.J. Zhao J. Weng C. Klibanski A. Activation of p53 by MEG3 Non-coding RNA. J. Biol. Chem. 2007 282 34 24731 24742 10.1074/jbc.M702029200 17569660
    [Google Scholar]
  67. Benetatos L. Hatzimichael E. Dasoula A. Dranitsaris G. Tsiara S. Syrrou M. Georgiou I. Bourantas K.L. CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes. Leuk. Res. 2010 34 2 148 153 10.1016/j.leukres.2009.06.019 19595458
    [Google Scholar]
  68. Sellers Z.P. Bolkun L. Kloczko J. Wojtaszewska M.L. Lewandowski K. Moniuszko M. Ratajczak M.Z. Schneider G. Increased methylation upstream of the MEG3 promotor is observed in acute myeloid leukemia patients with better overall survival. Clin. Epigenetics 2019 11 1 50 10.1186/s13148‑019‑0643‑z 30876483
    [Google Scholar]
  69. Zhao J. Dahle D. Zhou Y. Zhang X. Klibanski A. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J. Clin. Endocrinol. Metab. 2005 90 4 2179 2186 10.1210/jc.2004‑1848 15644399
    [Google Scholar]
  70. Gejman R. Batista D.L. Zhong Y. Zhou Y. Zhang X. Swearingen B. Stratakis C.A. Hedley-Whyte E.T. Klibanski A. Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J. Clin. Endocrinol. Metab. 2008 93 10 4119 4125 10.1210/jc.2007‑2633 18628527
    [Google Scholar]
  71. Zhang X. Gejman R. Mahta A. Zhong Y. Rice K.A. Zhou Y. Cheunsuchon P. Louis D.N. Klibanski A. Maternally expressed gene 3, an imprinted non-coding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res. 2010 70 6 2350 2358 10.1158/0008‑5472.CAN‑09‑3885 20179190
    [Google Scholar]
  72. Tang X. Zhou H. Liu Y. High expression of DLGAP5 indicates poor prognosis and immunotherapy in lung adenocarcinoma and promotes proliferation through regulation of the cell cycle. Dis. Markers 2023 2023 1 20 10.1155/2023/9292536 36712920
    [Google Scholar]
  73. Branchi V. García S.A. Radhakrishnan P. Győrffy B. Hissa B. Schneider M. Reißfelder C. Schölch S. Prognostic value of DLGAP5 in colorectal cancer. Int. J. Colorectal Dis. 2019 34 8 1455 1465 10.1007/s00384‑019‑03339‑6 31286215
    [Google Scholar]
  74. Chen M. Zhang S. Wang F. He J. Jiang W. Zhang L. DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target. J. Transl. Med. 2024 22 1 209 10.1186/s12967‑024‑04910‑8 38414025
    [Google Scholar]
  75. Batra R. Harder N. Gogolin S. Diessl N. Soons Z. Jäger-Schmidt C. Lawerenz C. Eils R. Rohr K. Westermann F. König R. Time-lapse imaging of neuroblastoma cells to determine cell fate upon gene knockdown. PLoS One 2012 7 12 e50988 10.1371/journal.pone.0050988 23251412
    [Google Scholar]
  76. Starkova T. Polyanichko A. Tomilin A.N. Chikhirzhina E. Structure and functions of HMGB2 protein. Int. J. Mol. Sci. 2023 24 9 8334 10.3390/ijms24098334 37176041
    [Google Scholar]
  77. Cui G. Cai F. Ding Z. Gao L. HMGB2 promotes the malignancy of human gastric cancer and indicates poor survival outcome. Hum. Pathol. 2019 84 133 141 10.1016/j.humpath.2018.09.017 30296520
    [Google Scholar]
  78. Neubert E.N. DeRogatis J.M. Lewis S.A. Viramontes K.M. Ortega P. Henriquez M.L. Buisson R. Messaoudi I. Tinoco R. HMGB2 regulates the differentiation and stemness of exhausted CD8+ T cells during chronic viral infection and cancer. Nat. Commun. 2023 14 1 5631 10.1038/s41467‑023‑41352‑0 37704621
    [Google Scholar]
  79. Seyedin S.M. Pehrson J.R. Cole R.D. Loss of chromosomal high mobility group proteins HMG1 and HMG2 when mouse neuroblastoma and Friend erythroleukemia cells become committed to differentiation. Proc. Natl. Acad. Sci. USA 1981 78 10 5988 5992 10.1073/pnas.78.10.5988 6458811
    [Google Scholar]
  80. Lebedev T.D. Vagapova E.R. Popenko V.I. Leonova O.G. Spirin P.V. Prassolov V.S. Two receptors, two isoforms, two cancers: Comprehensive analysis of KIT and TrkA expression in neuroblastoma and acute myeloid leukemia. Front. Oncol. 2019 9 1046 10.3389/fonc.2019.01046 31681584
    [Google Scholar]
  81. Sethi S.C. Singh R. Sahay O. Barik G.K. Kalita B. Unveiling the hidden gem: A review of long non-coding RNA NBAT-1 as an emerging tumor suppressor and prognostic biomarker in cancer. Cell. Signal. 2025 126 111525 10.1016/j.cellsig.2024.111525 39592019
    [Google Scholar]
  82. Wei L. Ling M. Yang S. Xie Y. Liu C. Yi W. Long non-coding RNA NBAT1 suppresses hepatocellular carcinoma progression via competitively associating with IGF2BP1 and decreasing c-Myc expression. Hum. Cell 2021 34 2 539 549 10.1007/s13577‑020‑00464‑1 33387362
    [Google Scholar]
  83. Wang D.L. Yuan P. Tian J.Y. Expression of long non-coding RNA NBAT1 is associated with the outcome of patients with non-small cell lung cancer. Rev. Assoc. Med. Bras. 2020 66 7 898 903 10.1590/1806‑9282.66.7.898 32844929
    [Google Scholar]
  84. Xue S. Wang S. Li J. Guan H. Jiang S. Guo Y. Li Q. LncRNA NBAT1 suppresses cell proliferation and migration via miR-346/GSK-3β axis in renal carcinoma. IUBMB Life 2019 71 11 1720 1728 10.1002/iub.2111 31298469
    [Google Scholar]
  85. Gao Y. Chen J. Low expression of lncRNA NBAT-1 promotes gastric cancer development and is associated with poor prognosis. J. BUON 2019 24 2 656 662 31128020
    [Google Scholar]
  86. Li X. Zhang H. Wu X. Long non-coding RNA DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1. Gene 2019 686 1 7 10.1016/j.gene.2018.10.065 30366080
    [Google Scholar]
  87. Wang H. Niu X. Jiang H. Mao F. Zhong B. Jiang X. Fu G. Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway. Aging (Albany NY) 2020 12 16 16021 16034 10.18632/aging.103374 32756011
    [Google Scholar]
  88. Zeng X. Hu Z. Ke X. Tang H. Wu B. Wei X. Liu Z. Long non-coding RNA DLX6-AS1 promotes renal cell carcinoma progression via miR-26a/PTEN axis. Cell Cycle 2017 16 22 2212 2219 10.1080/15384101.2017.1361072 28881158
    [Google Scholar]
  89. Zhao H. Xu Q. Long non-coding RNA DLX6-AS1 mediates proliferation, invasion and apoptosis of endometrial cancer cells by recruiting p300/E2F1 in DLX6 promoter region. J. Cell. Mol. Med. 2020 24 21 12572 12584 10.1111/jcmm.15810 32951317
    [Google Scholar]
  90. Zhu X. Ma X. Zhao S. Cao Z. DLX6-AS1 accelerates cell proliferation through regulating miR -497-5p/ SNCG pathway in prostate cancer. Environ. Toxicol. 2021 36 3 308 319 10.1002/tox.23036 33035382
    [Google Scholar]
  91. Zheng Q. Gu X. Yang Q. Chu Q. Dai Y. Chen Z. DLX6-AS1 is a potential biomarker and therapeutic target in cancer initiation and progression. Clin. Chim. Acta 2021 517 1 8 10.1016/j.cca.2021.02.006 33607068
    [Google Scholar]
  92. Hu Y. Sun H. Hu J. Zhang X. LncRNA DLX6-AS1 promotes the progression of neuroblastoma by activating STAT2 via targeting miR-506-3p. Cancer Manag. Res. 2020 12 7451 7463 10.2147/CMAR.S252521 32904436
    [Google Scholar]
  93. Zhang H. Xing M. Guo J. Zhao J. Chen X. Jiang Z. Zhang H. Dong Q. Long non-coding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway. Cancer Cell Int. 2019 19 1 313 10.1186/s12935‑019‑0968‑x 31787850
    [Google Scholar]
  94. Jia P. Wei E. Liu H. Wu T. Wang H. Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR -513c-5p/ PLK4 axis. IUBMB Life 2020 72 12 2627 2636 10.1002/iub.2392 33031637
    [Google Scholar]
  95. Xue C. Lv L. Jiang J. Li L. Promising long non-coding RNA DLX6-AS1 in malignant tumors. Am. J. Transl. Res. 2020 12 12 7682 7692 33437353
    [Google Scholar]
  96. Zhao Y. Li P. Strategies of LncRNA DLX6-AS1 on study and therapeutics. Front. Genet. 2022 13 871988 10.3389/fgene.2022.871988 35719380
    [Google Scholar]
  97. Sahu D. Ho S.Y. Juan H.F. Huang H.C. High-risk, expression-based prognostic long non-coding RNA signature in neuroblastoma. JNCI Cancer Spectr. 2018 2 2 pky015 10.1093/jncics/pky015 31360848
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673357175250401205951
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Regulatory Relationships between DNA Methylation and Long Non- coding RNAs in Neuroblastoma
Bentham Science Publishers ; https://doi.org/10.2174/0109298673357175250401205951
/content/journals/cmc/10.2174/0109298673357175250401205951
/content/journals/cmc/10.2174/0109298673357175250401205951
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  • Article Type:     Review Article
Keywords: prognosis ; RNA ; Neuroblastoma ; DNA methyltransferase ; long non-coding ; prognostic indicators

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